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High resolution cryo-EM maps of Human papillomavirus 16 reveal L2 location and heparin-induced conformational changesHigh resolution cryo-EM maps of Human papillomavirus 16 reveal L2 location and heparin-induced conformational changes
Structural highlights
FunctionVL1_HPV16 Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.[HAMAP-Rule:MF_04002][1] [2] [3] Publication Abstract from PubMedHuman papillomavirus (HPV) is a significant health burden and leading cause of virus-induced cancers. The current commercial vaccines are genotype specific and provide little therapeutic benefit to patients with existing HPV infections. Host entry mechanisms represent an excellent target for alternative therapeutics, but HPV receptor use, the details of cell attachment, and host entry are inadequately understood. Here we present near-atomic resolution structures of the HPV16 capsid and HPV16 in complex with heparin, both determined from cryoelectron micrographs collected with direct electron detection technology. The structures clarify details of capsid architecture for the first time, including variation in L1 major capsid protein conformation and putative location of L2 minor protein. Heparin binds specifically around the capsid icosahedral vertices and may recapitulate the earliest stage of infection, providing a framework for continuing biochemical, genetic, and biophysical studies. Cryoelectron Microscopy Maps of Human Papillomavirus 16 Reveal L2 Densities and Heparin Binding Site.,Guan J, Bywaters SM, Brendle SA, Ashley RE, Makhov AM, Conway JF, Christensen ND, Hafenstein S Structure. 2016 Dec 31. pii: S0969-2126(16)30391-4. doi:, 10.1016/j.str.2016.12.001. PMID:28065506[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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